Previous work by the applicant has shown depression of the ventilatory response to hypoxia and hypercapnia in severe asthma. This series of experiments is designed to a) define the hypoxic and hypercapnic drives of asthmatics as related to duration and severity of disease, b) study the effect of aminophylline, isoproterenal and corticosteroids on the ventilatory response to hypoxia in these patients, c) examine the effect of hypoxia and hypercapnia on the airways of these patients who have hyperreactive airways and d) evaluate the protective effect of animonphylline, isoporterenol, and corticosteroids on any changes in airway dynamics that are produced by hypoxia. The ventilatory response of normal and asthmatic subjects to progressive isocapnic hypoxia and the hyperoxic hypercapnia will be measured in a constant volume body plethysmograph. Responses will be related to the severity and duration of disease. Toward the end of each evaluation, forced expiratory flows, thoracic gas volume, and specific conductance will be measured. The changes in the measurements of airways dynamics will be compared to values obtained when alveolar gas tensions were normal. These two procedures will be carrid out in all subjects before and after single-blind administration of intravenous aminophylline, inhaled isoproterenal and oral corticosteroids. Measurements following appropriate placebo administration will also be perfomed. The effect of these parmacologic agents upon the hypoxic ventilatory drive in normals and in asthmatics will be evaluated. Their action during hypoxia will also be observed. Thus, this project will provide information about the effects of hypoxia and hypercapnia on the ventilatory controls and airways functions of normal human and asthmatic subjects. The beneficial effects of various pharmacologic agents commonly used in asthma upon abnormalities found will be evaluated.